title: Involvement of upregulated p53-induced death domain protein (PIDD) in neuronal apoptosis after rat traumatic brain injury.
abstract: Traumatic brain injury (TBI) initiates a series of complicated pathological events that could eventually lead to neuronal apoptosis. Recent studies indicated that p53 played a crucial role in neuronal apoptosis and regeneration following TBI. However, the detailed mechanism of p53-induced neuronal apoptosis in TBI remains largely elusive. In this study, we identified that p53-induced death domain protein (PIDD), whose transcription could be rapidly induced by p53 activation, was significantly upregulated after TBI. Western blot and immunohistochemistrical analyses revealed that the expression of PIDD was gradually increased, reached a peak at 3 days, and then decreased gradually to basal level after brain trauma. Further, double immunofluorescent analysis showed that PIDD was distributed predominantly in neurons, and the number of PIDD-positive neurons was significantly elevated in injured brain cortex. In addition, we found that PIDD was mainly distributed in active caspase-3-positive neurons, implicating a possible involvement of PIDD in the regulation of neuronal apoptosis during TBI. Finally, we showed that the expressions of p53 and Bax were altered correlatively with PIDD after brain trauma, implying that the upregulation of PIDD after TBI might be a result of p53 activation. Taken together, these findings suggested that PIDD might be an important regulator and potential therapeutic target of TBI.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wan
authors.forename: Junkang
authors.initials: J
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cao
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3